Novel ametantrone-amsacrine related hybrids as topoisomerase IIß poisons and cytotoxic agents.
Arch Pharm (Weinheim)
; 347(10): 728-37, 2014 Oct.
Article
em En
| MEDLINE
| ID: mdl-25042690
The precise definition of the structural requirements for effective topoisomerase II poisoning by drug molecules is still an elusive issue. In the attempt to better define a pharmacophoric pattern, we prepared several conjugates combining the chemical features of two well-known topoisomerase II poisons, amsacrine and ametantrone. Indeed, an appropriate fusion geometry, which entails the anthracenedione moiety of ametantrone appropriately connected to the methanesulfonamidoaniline side chain of amsacrine, elicits DNA-intercalating properties, the capacity to inhibit the human topoisomerase IIß isoform, and cytotoxic activity resembling that of the parent compounds. In addition, the properties of the lateral groups linked to the anthracenedione group play an important role in modulating DNA binding and cell cytotoxicity. Among the compounds tested, 10, 11, and 19 appear to be promising for further development.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Amsacrina
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Desenho de Fármacos
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Mitoxantrona
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Proteínas de Ligação a DNA
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Inibidores da Topoisomerase II
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Neoplasias
Limite:
Humans
Idioma:
En
Revista:
Arch Pharm (Weinheim)
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Itália